Modeling the excitability of mammalian nerve fibers: Influence of afterpotentials on the recovery cycle
Modeling the excitability of mammalian nerve fibers: Influence of afterpotentials on the recovery cycle
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DOI：
10.1152/jn.00353.2001
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发表时间：
2002-02-01
影响因子：
2.5
通讯作者：
Grill, WM
中科院分区：
文献类型：
--
作者：
McIntyre, CC;Richardson, AG;Grill, WM
人类神经纤维表现出一种独特的阈值波动模式，这种波动遵循一个被称为恢复周期的单一动作电位。我们开发了哺乳动物运动神经纤维的几何和电精确模型，以深入了解轴突兴奋性变化和调节恢复周期的生物物理机制。本研究中开发的模型包含双缆结构，明确表示轴突的Ranvier节、旁结节和节间节节，以及有限阻抗髓鞘。这些模型能够再现哺乳动物有髓神经纤维兴奋特性的广泛实验数据。节点上离子通道的精确表示（基于人类、猫和大鼠的实验研究）和将旁阳极、节间和髓鞘的几何形状与测量形态学相匹配（需要双电缆表示）相结合，才能使模型行为与实验数据相匹配。在动作电位之后，模型同时产生去极化（DAP）和超极化（AHP）后电位。该模型的结果支持这样的假设，即主动（持续的Na+通道激活）和被动（通过旁结密封释放节间轴膜）机制都有助于DAP，而AHP仅通过主动（缓慢的K+通道激活）机制产生。纤维的恢复周期取决于DAP和AHP，以及快速Na+电导激活和失活的时间常数。我们提出，实验记录的运动和感觉神经纤维的动作电位形状、强度-持续时间关系和恢复周期的差异可归因于它们的节Na+电导的动力学差异。
Human nerve fibers exhibit a distinct pattern of threshold fluctuation following a single action potential known as the recovery cycle. We developed geometrically and electrically accurate models of mammalian motor nerve fibers to gain insight into the biophysical mechanisms that underlie the changes in axonal excitability and regulate the recovery cycle. The models developed in this study incorporated a double cable structure, with explicit representation of the nodes of Ranvier, paranodal, and internodal sections of the axon as well as a finite impedance myelin sheath. These models were able to reproduce a wide range of experimental data on the excitation properties of mammalian myelinated nerve fibers. The combination of an accurate representation of the ion channels at the node (based on experimental studies of human, cat, and rat) and matching the geometry of the paranode, internode, and myelin to measured morphology (necessitating the double cable representation) were needed to match the model behavior to the experimental data. Following an action potential, the models generated both depolarizing (DAP) and hyperpolarizing (AHP) afterpotentials. The model results support the hypothesis that both active (persistent Na+ channel activation) and passive (discharging of the internodal axolemma through the paranodal seal) mechanisms contributed to the DAP, while the AHP was generated solely through active (slow K+ channel activation) mechanisms. The recovery cycle of the fiber was dependent on the DAP and AHP, as well as the time constant of activation and inactivation of the fast Na+ conductance. We propose that experimentally documented differences in the action potential shape, strength-duration relationship, and the recovery cycle of motor and sensory nerve fibers can be attributed to kinetic differences in their nodal Na+ conductances.